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1.
Curr Rheumatol Rep ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913291

RESUMO

PURPOSE OF REVIEW: This review aims to summarize the evolution and recent developments in the classification of ANCA associated vasculitis (AAV) and to summarize evaluations of the 2022 ACR/EULAR classification criteria of AAV in several cohorts. RECENT FINDINGS: The classification of AAV has been a field of controversy for some time. The parallel existence of classification criteria and disease definitions produced some overlap in classification, leading to challenges when comparing different cohorts. The 2022 ACR/EULAR classification criteria derived from the largest study ever conducted in vasculitis account for significant changes in vasculitis classification with the integration of ANCA and modern imaging. These criteria show good performance compared to previous ones but also raise questions as ANCA serotypes have substantial impact on classification. In addition, there are some discrepancies with earlier agreed histopathological features of AAV disease phenotypes. During the last 35 years, several sets of classification criteria have evolved to facilitate epidemiologic studies and clinical trials in AAV. While some of these criteria have been in use for many years, they were criticized due to either not using ANCA or not integrating surrogate markers for vasculitis but also due to overlapping when used in parallel. The long-awaited new ACR/EULAR criteria for AAV were published in 2022 and are the result of a large international study, introducing for the first time ANCA and modern imaging in the classification of AAV. Though the criteria show good performance, they bring several other challenges with practical application.

2.
RMD Open ; 10(2)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38580345

RESUMO

OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV. METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively. RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Anticorpos Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Mieloblastina/genética , Genótipo , Recidiva
3.
RMD Open ; 10(2)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599652

RESUMO

OBJECTIVES: To determine the incidence rate (IR) of myocardial infarction (MI), relative risk of MI, and impact of incident MI on mortality in individuals with biopsy-confirmed giant cell arteritis (GCA). METHODS: MIs in individuals diagnosed with GCA 1998-2016 in Skåne, Sweden were identified by searching the SWEDEHEART register, a record of all patients receiving care for MI in a coronary care unit (CCU). The regional diagnosis database, with subsequent case review, identified GCA patients receiving care for MI outside of a CCU. A cohort of 10 reference subjects for each GCA case, matched for age, sex and area of residence, was used to calculate the incidence rate ratio (IRR) of MI in GCA to that in the general population. RESULTS: The GCA cohort comprised 1134 individuals. During 7958 person-years of follow-up, 102 were diagnosed with incident MI, yielding an IR of 12.8 per 1000 person-years (95% CI 10.3 to 15.3). The IR was highest in the 30 days following GCA diagnosis and declined thereafter. The IRR of MI in GCA to that of the background population was 1.29 (95% CI 1.05 to 1.59). Mortality was higher in GCA patients who experienced incident MI than in those without MI (HR 2.8; 95% CI 2.2 to 3.6). CONCLUSIONS: The highest incidence of MI occurs within the 30 days following diagnosis of GCA. Individuals with GCA have a moderately increased risk of MI compared with a reference population. Incident MI has a major impact on mortality in GCA.


Assuntos
Arterite de Células Gigantes , Infarto do Miocárdio , Humanos , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/epidemiologia , Suécia/epidemiologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Biópsia
4.
Arthritis Rheumatol ; 76(7): 1120-1129, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38343337

RESUMO

OBJECTIVE: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN). METHODS: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed. RESULTS: Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 µmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. CONCLUSION: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 µmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.


Assuntos
Poliarterite Nodosa , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Europa (Continente)/epidemiologia , Idoso , América do Norte/epidemiologia , Japão/epidemiologia , Adulto Jovem , Proteinúria/etiologia , Recidiva , Taxa de Sobrevida
5.
RMD Open ; 10(1)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316490

RESUMO

OBJECTIVE: Immunoglobulin A vasculitis (IgAV) is the most prevalent primary childhood vasculitis in Sweden, but is considerably rarer in adults. This study aims to describe the epidemiology, clinical characteristics and renal outcome of adult-onset IgAV in Skåne, Sweden. METHODS: The study area consisted of Skåne, the southernmost region of Sweden, with a population ≥18 years of 990 464 on 31 December 2010. Adult patients assigned the International Classification of Diseases-10 code for IgAV (D69.0) from 2000 through 2019 were retrospectively identified in a population-based database. Medical records were reviewed to validate the diagnosis of IgAV and extract data. Only patients with clinical manifestations of IgAV and biopsy-confirmed disease were included. The annual incidence and point prevalence of biopsy-confirmed IgAV were estimated. RESULTS: Fifty-nine patients (19 women) were classified as having adult-onset IgAV. The incidence was 3 per 1 000 000 and was higher among men than women (4 vs 2/1 000 000, p=0.004). Ninety-seven per cent of patients presented with non-thrombocytopenic purpura, 78% with renal involvement, 59% with arthritis/arthralgia and 39% with gastrointestinal symptoms. Fifteen per cent developed chronic kidney disease stage ≥G3 a and one patient progressed to end-stage kidney disease during follow-up. CONCLUSION: Adult-onset IgAV is rare in southern Sweden with the incidence higher in men than in women. IgAV frequently affects the kidneys and leads to chronic kidney disease in adults, although the long-term renal outcome appears favourable compared with other small-vessel vasculitides affecting the kidneys.


Assuntos
Vasculite por IgA , Insuficiência Renal Crônica , Vasculite , Masculino , Adulto , Humanos , Feminino , Criança , Vasculite por IgA/diagnóstico , Vasculite por IgA/epidemiologia , Estudos Retrospectivos , Suécia/epidemiologia , Imunoglobulina A , Vasculite/epidemiologia , Biópsia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38310345

RESUMO

OBJECTIVE: To investigate the relation between biomarkers associated with metabolism and subsequent development of giant cell arteritis (GCA). METHOD: Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30447), who were subsequently diagnosed with GCA, were identified in a structured process. Matched GCA-free controls were selected from the study cohort. Baseline plasma samples were analyzed using the antibody-based OLINK proteomics metabolism panel (92 metabolic proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. RESULTS: There were 95 cases with a confirmed incident diagnosis of GCA (median 12.0 years after inclusion). Among biomarkers with a priori hypotheses, Adhesion G protein-coupled receptor E2 (ADGRE2) was positively associated (odds ratio (OR) per standard deviation (SD) 1.67; 95% CI 1.08-2.57), and Fructose-1,6-bisphosphatase 1 (FBP1) negatively associated (OR per SD 0.59; 95% CI 0.35-0.99) with GCA. In particular, ADGRE2 levels were associated with subsequent GCA in the subset sampled <8.5 years before diagnosis. For meteorin-like protein (Metrnl), the highest impact on the risk of GCA was observed in those sampled closest to diagnosis with a decreasing trend with longer time to GCA (p= 0.03). In the hypothesis generating analyses, elevated levels of receptor tyrosine-like orphan receptor 1 (ROR1) were associated with subsequent GCA. CONCLUSION: Biomarkers identified years before clinical diagnosis indicated a protective role of gluconeogenesis (FBP1) and an association with macrophage activation (ADGRE2 and Metrnl) and proinflammatory signals (ROR1) for development of GCA.

7.
Arthritis Res Ther ; 26(1): 37, 2024 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-38281009

RESUMO

BACKGROUND: The etiology of giant cell arteritis (GCA) and its predictors are incompletely understood. Previous studies have indicated reduced risk of future development of GCA in individuals with obesity and/or diabetes mellitus. There is limited information on blood lipids before the onset of GCA. The objective of the study was to investigate the relation between apolipoprotein levels and future diagnosis of GCA in a nested case-control analysis. METHODS: Individuals who developed GCA after inclusion in a population-based health survey (the Malmö Diet Cancer Study; N = 30,447) were identified by linking the health survey database to the local patient administrative register and the national patient register. A structured review of medical records was performed. Four controls for every validated case, matched for sex, year of birth, and year of screening, were selected from the database. Anthropometric measures, self-reported physical activity, based on a comprehensive, validated questionnaire, and non-fasting blood samples had been obtained at health survey screening. Concentrations of apolipoprotein A-I (ApoA-I) and apolipoprotein B (ApoB) in stored serum were measured using an immunonephelometric assay. Potential predictors of GCA were examined in conditional logistic regression models. RESULTS: There were 100 cases with a confirmed clinical diagnosis of GCA (81% female; mean age at diagnosis 73.6 years). The median time from screening to diagnosis was 12 years (range 0.3-19.1). The cases had significantly higher ApoA-I at baseline screening compared to controls (mean 168.7 vs 160.9 mg/dL, odds ratio [OR] 1.57 per standard deviation (SD); 95% confidence interval [CI] 1.18-2.10) (SD 25.5 mg/dL). ApoB levels were similar between cases and controls (mean 109.3 vs 110.4 mg/dL, OR 0.99 per SD; 95% CI 0.74-1.32) (SD 27.1 mg/dL). The ApoB/ApoA1 ratio tended to be lower in cases than in controls, but the difference did not reach significance. The association between ApoA-I and GCA development remained significant in analysis adjusted for body mass index and physical activity (OR 1.48 per SD; 95% CI 1.09-1.99). CONCLUSION: Subsequent development of GCA was associated with significantly higher levels of ApoA-I. These findings suggest that a metabolic profile associated with lower risk of cardiovascular disease may predispose to GCA.


Assuntos
Arterite de Células Gigantes , Humanos , Feminino , Idoso , Masculino , Arterite de Células Gigantes/diagnóstico , Fatores de Risco , Apolipoproteína A-I , Estudos de Casos e Controles , Apolipoproteínas , Apolipoproteínas B
8.
Ann Rheum Dis ; 83(1): 112-120, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37907255

RESUMO

OBJECTIVES: This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. METHODS: Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. RESULTS: A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. CONCLUSIONS: In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/epidemiologia , Granulomatose com Poliangiite/complicações , Confiabilidade dos Dados , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Poliangiite Microscópica/tratamento farmacológico , Poliangiite Microscópica/epidemiologia , Anticorpos Anticitoplasma de Neutrófilos , Sistema de Registros , Armazenamento e Recuperação da Informação
9.
Ann Rheum Dis ; 83(1): 30-47, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36927642

RESUMO

BACKGROUND: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. METHODS: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. RESULTS: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. CONCLUSIONS: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Granulomatose com Poliangiite/diagnóstico , Poliangiite Microscópica/diagnóstico , Indução de Remissão , Rituximab/uso terapêutico , Guias de Prática Clínica como Assunto
10.
Rheumatol Adv Pract ; 7(3): rkad071, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37675201

RESUMO

Objectives: To study if active sun exposure among women affects the risk of developing GCA or PMR in a prospective cohort study with restricted latitudinal variability. Methods: We linked the response to questions relating to sun exposure from the Melanoma Inquiry in Southern Sweden (MISS) prospective cohort study in women to the risk of developing GCA or PMR. Healthcare data were gathered from the Skåne Healthcare Register (SHR), covering all public healthcare consultations. The direct effect of active sun exposure on the risk of developing GCA or PMR was assessed using Cox proportional hazards models adjusted for covariates based on a directed acyclic graph. Results: A total of 14 574 women were included in the study; 601 women were diagnosed with GCA or PMR (144 and 457, respectively) during the follow-up time. Women with moderate or high sun exposure were not less likely to develop GCA or PMR compared with women that indicated they avoided sun exposure [hazard ratio (HR) 1.2 (CI 0.9, 1.6) and 1.3 (0.9, 1.9), respectively] when adjusted for diabetes, hyperlipidaemia, hypertension, smoking, obesity and stratified by age. Similar patterns were observed when studying only GCA [HR 1.2 (CI 0.7, 2.3) and 1.3 (0.7, 2.6)] and only PMR [HR 1.3 (CI 0.9, 1.8) and 1.4 (0.9, 2.0)]. Conclusion: Active sun exposure did not affect the risk of developing GCA or PMR in women in a cohort with restricted latitudinal variability.

11.
Artigo em Inglês | MEDLINE | ID: mdl-37758240

RESUMO

OBJECTIVE: To evaluate the ACR/EULAR 2022 criteria for AAV classification and compare it to the EMA algorithm and to classification based only on ANCA serology. METHODS: In the analysis, 374 cases (47% female) were classified according to EMA algorithm, ANCA serology, and ACR/EULAR criteria. The agreement rate was calculated using the kappa (κ) statistic. RESULTS: Under EMA, 192 patients were classified as GPA, 159 as MPA, and 23 as EGPA. The ACR/EULAR criteria classified 199 patients as GPA, 136 as MPA, and 22 as EGPA. Four patients (1.1%) met criteria of two disease categories, and thirteen (3.5%) were unclassifiable. The observed agreement between EMA and ACR/EULAR was 85% for GPA, 75% for MPA, and 96% for EGPA. The unweighted κ statistic was 0.66 (95% CI 0.60-0.74). Of the 188 PR3-ANCA-positive patients, 186 (98.9%) were classified as GPA using ACR/EULAR criteria, and 135 of 161 (83.8%) MPO-ANCA-positive patients were classified as MPA. With a classification solely based on ANCA-specificity, agreement with ACR/EULAR was 99% for GPA and 88% for MPA. CONCLUSIONS: EMA and ACR/EULAR classification give similar results. A small proportion of patients cannot be classified or fall into two categories. Some patients exhibiting granuloma, a key feature of GPA, are nevertheless classified as MPA, conflicting with the current view of histopathology of AAV. There is high agreement of ANCA-based classification with that of ACR/EULAR, reflected in the considerable weight granted to ANCA in the new criteria. These crucial elements within the new criteria necessitate a consensus discussion among field experts.

12.
RMD Open ; 9(1)2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36894194

RESUMO

OBJECTIVE: To update the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in a defined geographical area of southern Sweden. METHODS: The study area comprised 14 municipalities with a combined adult population (≥18 years) of 623 872 in 2019. All cases diagnosed with AAV in 1997-2019 in the study area were included in the estimate of incidence. Diagnosis of AAV was verified by case record review, and cases were classified using the European Medicines Agency algorithm. Point prevalence was estimated on 01 January 2020. RESULTS: Three hundred and seventy-four patients (median age 67.5 years, 47% female) were diagnosed with new-onset AAV during the study period. One hundred and ninety-two were classified as granulomatosis with polyangiitis (GPA), 159 as microscopic polyangiitis (MPA) and 23 as EGPA. The average annual incidence/million adults was 30.1 (95% CI 27.0 to 33.1) for AAV: 15.4 (95% CI 13.3 to 17.6) for GPA, 12.8 (95% CI 10.8 to 14.8) for MPA and 1.8 (95% CI 1.1 to 2.6) for eosinophilic GPA (EGPA). Incidence was stable during the study period, 30.3/million 1997-2003, 30.4/million 2004-2011 and 29.5/million 2012-2019. The incidence increased with age and was highest in age group 70-84 years (96/million adults). On 1 January 2020, the prevalence was 428/million adults and was higher in males than in females (480 vs 378/million). CONCLUSIONS: The incidence of AAV in southern Sweden was found stable over the course of 23 years; while the prevalence has increased, which might indicate better management and treatment of AAV resulting in improved survival.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Adulto , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Prevalência , Suécia/epidemiologia , Incidência , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Granulomatose com Poliangiite/epidemiologia , Poliangiite Microscópica/epidemiologia , Poliangiite Microscópica/terapia
13.
J Rheumatol ; 50(9): 1145-1151, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36642436

RESUMO

OBJECTIVE: To investigate the occurrence of cardiovascular events (CVEs) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, China, Turkey, Russia, the United Kingdom, and the USA. METHODS: Patients with a definite diagnosis of AAV who were followed for ≥ 3 months and had sufficient documentation were included. Data on myocardial infarction (MI) and stroke were collected retrospectively from tertiary vasculitis centers. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Over a median follow-up of 62.0 months (IQR 22.6-100.0), CVEs (mostly MIs) occurred in 245 (10.7%) of 2286 patients with AAV, with a higher frequency in China and the UK. On multivariate regression analysis, older age (55-64.9 yrs, HR 2.93, 95% CI 1.99-4.31), smoking (HR 1.98, 95% CI 1.48-2.64), Chinese origin (HR 4.24, 95% CI 3.07-5.85), and pulmonary (HR 1.50, 95% CI 1.09-2.06) and kidney (HR 3.02, 95% CI 2.08-4.37) involvement were independent variables associated with a higher occurrence of CVEs. CONCLUSION: We showed that geographic region and both traditional and disease-specific (kidney involvement in particular) factors were independently associated with CVEs. Proper assessment and management of modifiable cardiovascular (CV) risk factors are essential for prevention of CV morbidity in patients with AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Estudos Retrospectivos , Rim , Fatores de Risco
14.
Arthritis Rheumatol ; 75(6): 996-1006, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36533851

RESUMO

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a chronic relapsing condition with unknown etiology. To gain insight into the molecular processes underlying the disease, we examined biomarkers in blood samples collected prior to symptom onset. METHODS: The National Patient Register and Cause of Death register were searched for AAV-related International Classification of Diseases, Ninth Revision and Tenth Revision codes and linked to the registers from 5 biobanks. Eighty-five AAV patients with samples predating symptom onset of AAV were identified. For each case of AAV, 2 matched controls were included. Proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA expression levels were analyzed using enzyme-linked immunosorbent assays. Using an Olink Inflammation panel, 73 of 92 proteins were included after quality control. Data were replicated in a second cohort of 48 presymptomatic individuals and 96 controls. RESULTS: Of the 20 proteins with the lowest P values in the original cohort, 7 were replicated in the second cohort and 5 proteins were found to be significant between the groups in a meta-analysis. Eleven different pathways were identified in network enrichment analyses and were found to be significant in both cohorts. Stratification of samples obtained ≤5 years before symptom onset showed significant levels of CCL23, vascular endothelial growth factor A, and hepatocyte growth factor, which were also increased at borderline significant levels in the replication cohort (interleukin-6 was found to be significantly increased in the replication cohort). In presymptomatic AAV patients, 6 proteins were associated with MPO-ANCA positivity, and 7 proteins were associated with PR3-ANCA positivity. CONCLUSION: To our knowledge, this is the first study to identify protein markers preceding symptom onset in AAV patients. These findings set the stage for further research into the underlying cellular and molecular mechanisms in the pathogenesis of AAV and the diversification of patients into PR3-ANCA+ and MPO-ANCA+ subphenotypes.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Mieloblastina , Fator A de Crescimento do Endotélio Vascular , Peroxidase
15.
Rheumatology (Oxford) ; 62(6): 2304-2311, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36255228

RESUMO

OBJECTIVE: To investigate the relation between biomarkers of inflammation and subsequent development of GCA. METHOD: Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30 447), established 1991-96, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth and year of screening were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on eigenvalues, proteins with a factor loading of >0.50 were investigated. RESULTS: Ninety-four cases with a confirmed incident diagnosis of GCA (median 11.9 years after inclusion) were identified. Among biomarkers with a priori hypotheses, IFN-γ was positively associated with GCA [odds ratio (OR) per s.d. 1.52; 95% CI 1.00, 2.30]. Eight biomarkers in the hypothesis-generating analyses were significantly associated with development of GCA. Among these, higher levels of IFN-γ (OR 2.37; 95% CI 1.14, 4.92) and monocyte chemotactic protein 3 (MCP3) (OR 4.27; 95% CI 1.26, 14.53) were particularly associated with increased risk of GCA in the subset sampled <8.5 years before diagnosis. Several other proteins known to be important for T cell function were also associated with GCA in these analyses, e.g. CXCL9, IL-2, CD40 and CCL25. CONCLUSION: Elevated IFN-γ levels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.


Assuntos
Arterite de Células Gigantes , Humanos , Arterite de Células Gigantes/complicações , Estudos Prospectivos , Biomarcadores , Inflamação/complicações , Proteínas Sanguíneas
16.
Front Med (Lausanne) ; 9: 1058600, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465919

RESUMO

Giant cell arteritis (GCA), the most common non-infectious vasculitis, mainly affects elderly individuals. The disease usually affects the aorta and its main supra-aortic branches causing both general symptoms of inflammation and specific ischemic symptoms because of the limited blood flow due to arterial structural changes in the inflamed arteries. The pathogenesis of the GCA is complex and includes a dysregulated immune response that affects both the innate and the adaptive immunity. During the last two decades several studies have investigated interactions among antigen-presenting cells and lymphocytes, which contribute to the formation of the inflammatory infiltrate in the affected arteries. Toll-like receptor signaling and interactions through the VEGF-Notch-Jagged1 pathway are emerging as crucial events of the aberrant inflammatory response, facilitating among others the migration of inflammatory cells to the inflamed arteries and their interactions with the local stromal milieu. The increased use of checkpoint inhibitors in cancer immunotherapy and their immune-related adverse events has fed interest in the role of checkpoint dysfunction in GCA, and recent studies suggest a dysregulated check point system which is unable to suppress the inflammation in the previously immune-privileged arteries, leading to vasculitis. The role of B-cells is currently reevaluated because of new reports of considerable numbers of plasma cells in inflamed arteries as well as the formation of artery tertiary lymphoid organs. There is emerging evidence on previously less studied cell populations, such as the neutrophils, CD8+ T-cells, T regulatory cells and tissue residing memory cells as well as for stromal cells which were previously considered as innocent bystanders. The aim of this review is to summarize the evidence in the literature regarding the cell populations involved in the pathogenesis of GCA and especially in the context of an aged, immune system.

17.
Kidney Int Rep ; 7(8): 1745-1757, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35967106

RESUMO

The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.

18.
Microorganisms ; 10(8)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-36013990

RESUMO

Microbiota has been associated with autoimmune diseases, with nasal Staphylococcus aureus being implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Little is known about the role of oral microbiota in AAV. In this study, levels of IgG antibodies to 53 oral bacterial species/subspecies were screened using immunoblotting in plasma/serum in pre-symptomatic AAV-individuals (n = 85), matched controls, and established AAV-patients (n = 78). Saliva microbiota from acute-AAV and controls was sequenced from 16s rDNA amplicons. Information on dental status was extracted from a national register. IgG levels against oral bacteria were lower in established AAV versus pre-AAV and controls. Specifically, pre-AAV samples had, compared to controls, a higher abundance of periodontitis-associated species paralleling more signs of periodontitis in established AAV-patients than controls. Saliva microbiota in acute-AAV showed higher within-sample diversity but fewer detectable amplicon-sequence variants and taxa in their core microbiota than controls. Acute-AAV was not associated with increased abundance of periodontal bacteria but species in, e.g., Arthrospira, Staphylococcus, Lactobacillus, and Scardovia. In conclusion, the IgG profiles against oral bacteria differed between pre-AAV, established AAV, and controls, and microbiota profiles between acute AAV and controls. The IgG shift from a pre-symptomatic stage to established disease cooccurred with treatment of immunosuppression and/or antibiotics.

19.
J Rheumatol ; 49(9): 1031-1036, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35649553

RESUMO

OBJECTIVE: The diagnostic yield of sural nerve biopsy (SNB) in vasculitis is uncertain. Our aim was to document relevant characteristics of patients undergoing SNB in the investigation of vasculitis; determine the diagnostic yield; relate positive biopsy findings to patient demographic, laboratory, and clinical variables; and to calculate the rate of surgical complications. METHODS: Patients with suspected vasculitis that underwent SNB as part of diagnostic evaluation at academic medical centers in Sweden and the United Kingdom were identified by searching local pathology databases and clinic registers. A structured review of medical case records and pathology reports was conducted. Histological findings were categorized as definite, probable, or no vasculitis in accordance with the 2015 Brighton Collaboration reinterpretation and update of the Peripheral Nerve Society guidelines for vasculitic neuropathy. Definite and probable findings were considered positive for vasculitis. RESULTS: Ninety-one patients that underwent SNB were identified (45% female). Forty (44%) patients showed histological evidence of vasculitis: 14 definite and 26 probable. A concomitant muscle biopsy conducted in 10 patients did not contribute to the diagnostic yield. Positive antineutrophil cytoplasmic antibody test, organ involvement other than the nervous system, and a longer biopsy sample were associated with a positive biopsy. The reported surgical complication rate was 15%. CONCLUSION: SNB of sufficient length is a useful procedure to confirm a diagnosis of vasculitis.


Assuntos
Doenças do Sistema Nervoso Periférico , Vasculite , Humanos , Feminino , Masculino , Anticorpos Anticitoplasma de Neutrófilos , Nervo Sural/patologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Vasculite/complicações , Biópsia
20.
J Intern Med ; 292(5): 717-732, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35612524

RESUMO

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease affecting people older than 50 years and is 2-3 times more common in women. The most common symptoms are pain and morning stiffness in the shoulder and pelvic girdle and the onset may be acute or develop over a few days to weeks. General symptoms such as fatigue, fever and weight loss may occur, likely driven by systemic IL-6 signalling. The pathology includes synovial and periarticular inflammation and muscular vasculopathy. A new observation is that PMR may appear as a side effect of cancer treatment with checkpoint inhibitors. The diagnosis of PMR relies mainly on symptoms and signs combined with laboratory markers of inflammation. Imaging modalities including ultrasound, magnetic resonance imaging and positron emission tomography with computed tomography are promising new tools in the investigation of suspected PMR. However, they are still limited by availability, high cost and unclear performance in the diagnostic workup. Glucocorticoid (GC) therapy is effective in PMR, with most patients responding promptly to 15-25 mg prednisolone per day. There are challenges in the management of patients with PMR as relapses do occur and patients with PMR may need to stay on GC for extended periods. This is associated with high rates of GC-related comorbidities, such as diabetes and osteoporosis, and there are limited data on the use of disease-modifying antirheumatic drugs and biologics as GC sparing agents. Finally, PMR is associated with giant cell arteritis that may complicate the disease course and require more intense and prolonged treatment.


Assuntos
Antirreumáticos , Produtos Biológicos , Arterite de Células Gigantes , Polimialgia Reumática , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Biomarcadores , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Inflamação/complicações , Interleucina-6 , Polimialgia Reumática/complicações , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Prednisolona/uso terapêutico
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